Cytotoxic T cell and neutralizing antibody responses to human immunodeficiency virus type 1 envelope with a combination vaccine regimen. AIDS Vaccine Evaluation Group.
Effective human immunodeficiency virus (HIV) vaccination may require induction of neutralizing antibodies (NAs) and CD8+ cytotoxic T lymphocytes (CTL) to prevent transmission and control early infection. Recombinant envelope proteins induce NAs but rarely CD8+ CTL responses, and vaccinia vectors containing HIV-1 envelope elicit CD8+ cytotoxicity but few NAs. To benefit from both approaches, 56 vaccinia-naive subjects were randomized to a regimen of priming with recombinant vaccinia gp160LAI and boosting with recombinant gp120SF-2, gp120LAI, gp120MN, or gp160MN. Of 51 persons for whom assays were done, 26 demonstrated envelope-specific CTL. Boosting with gp120, compared with gp160, elicited significantly more NAs and CD4-blocking antibodies. Neutralization of the homologous and heterologous HIV-1 laboratory strains occurred in all subjects receiving vac/env and gp120 and was detectable in 91% of the subjects for >6 months. Thus, vaccine regimens in which one component elicits primarily CTL and the other NAs offer promise for the development of an effective HIV-1 vaccine strategy.
Corey
L
L
Infectious Diseases Program, University of Washington School of Medicine, Seattle, USA.
McElrath
M J
MJ
Weinhold
K
K
Matthews
T
T
Stablein
D
D
Graham
B
B
Keefer
M
M
Schwartz
D
D
Gorse
G
G
D016915:AIDS Vaccines / Q000276:immunology; D000293:Adolescent; D000328:Adult; D019138:Antibodies, Blocking / Q000276:immunology; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology; D000915:Antibody Affinity / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004311:Double-Blind Method; D005260:Female; D015483:HIV Antibodies / Q000032:analysis / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017778:Vaccines, Combined / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D019138:Antibodies, Blocking; D000914:Antibodies, Viral; D015704:CD4 Antigens; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011994:Recombinant Proteins; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic